AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Background

Ataxia-telangiectasia (AT) is a genetic disease characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, and recurrent respiratory and sinus infections. The first case described in the literature was a 9-year-old with progressive cerebellar ataxia and bilateral oculocutaneous telangiectasia reported in 1941 by Madame Louis-Bar. Initially known as the Louis-Bar syndrome, the term ataxia-telangiectasia was introduced in 1958 by Boder et al, who recorded the clinical features and recognized the familial incidence proposing an autosomal recessive mode of inheritance for the disease. The disease is sometimes referred to as Boder-Sedgwick syndrome.

Progressive cerebellar ataxia usually becomes clinically apparent when the child begins to walk. The ataxia affects station, gait, and intention. Telangiectasia of the bulbar conjunctiva first appears at 3-7 years and, subsequently, involves the malar areas, palate, ears, and antecubital and popliteal spaces. Other features of this syndrome include retardation of growth, dysarthric speech, dry coarse hair and skin, and mental retardation after age 10 years. The complete syndrome includes hypoplasia of the thymus associated with defective T-cell function and decreased levels of circulating immunoglobulin. Recurrent respiratory tract and sinus infections are common, frequently causing death in adolescence or young adulthood. A high incidence of malignancies occurs, particularly leukemia and Hodgkins lymphoma.

Ataxia-telangiectasia combines central nervous system disease with an oculocutaneous anomaly, fulfilling the criteria for classification within the phakomatoses group of diseases.

Pathophysiology

Ataxia-telangiectasia mainly is due to a defect in a DNA processing or repair protein. The cerebellar and extrapyramidal systems are the most severely affected. This syndrome is characterized by a severe loss of Purkinje cells, and to a lesser degree, the basket and granular cells of the cerebellar cortex. Other pathological changes include cerebellar cortical atrophy, diffuse fibrillary gliosis, and degeneration of the anterior horn cells of the spinal cord. Studies have revealed reduced levels of cerebellar neurotransmitters including phosphoethanolamine, gamma-aminobutyric acid (GABA), and glutamic acid.

Frequency

United States

True incidence of AT is unknown. Although the disease is rare, prevalence has been estimated at about 1 in 40,000-50,000.

Mortality/Morbidity

Increased susceptibility to cancer contributes to early mortality in one third to one half of cases. The cause of death in more than 50% of affected patients is recurrent respiratory infections. Ataxia-telangiectasia is an autosomal recessive syndrome in which cancers develop in affected homozygotes at a rate approximately 100 times higher than in unaffected age-matched subjects. Retrospective studies have shown that persons heterozygous for the ataxia-telangiectasia gene, who make up about 1% of the general population, also have an excess risk of cancer, particularly breast cancer in women. Patients with ataxia-telangiectasia and cells derived from homozygotes and heterozygotes are unusually sensitive to ionizing radiation.

Sex

Males and females are affected equally.

Age

The mean age of patients with AT at the time of presentation is 2.5-7 years.

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

History

The syndrome of AT is characterized by pathological changes in various systems of the body. Clinically, the central nervous system, eye, skin, upper and lower respiratory tracts, immune system, and viscera are involved.

• Central nervous system
• • Cerebellar and extrapyramidal systems are the most affected.
  • Truncal ataxia is the first presenting symptom of the syndrome and usually appears after the child starts to walk. The first manifestations of truncal ataxia are swaying of the head and trunk on standing and even sitting. The ataxia is progressive and is accompanied by loss of deep tendon reflexes, dystonia, drooling, and dysarthria. Motor function continues to deteriorate, and, by age 10 years, it leads to serious disability, making the use of a wheelchair necessary.
  • Mental changes are not detectable in the earlier stages of the disease. As the child grows older, deterioration in mental processes occurs with slowing of reactions and lack of responsiveness. Evidence of mental retardation becomes apparent as the disease progresses.
• Eye
• • Telangiectasia of the conjunctiva has a later onset than ataxia and usually appears at age 3-7 years. The telangiectasia is first noted in the interpalpebral bulbar conjunctiva away from the limbus. Eventually the ocular telangiectasia becomes generalized and simulates a conjunctivitis.
  • Oculomotor abnormalities appear early in the disease and consist of an inability to execute voluntary gaze movements rapidly or on command. Version movements are not restricted, but, on command gaze, they are performed in a halting dyssynergistic fashion. Nystagmus may reduce distance visual acuity and impair fixation. The vestibulo-ocular movements are preserved, but there is a poor ability to initiate saccades. Convergence ability frequently is impaired.
  • Visual acuity, pupillary reflex responses, and fundi are normal.
• Skin
• • Cutaneous telangiectasia becomes apparent at 3-7 years. It is first seen on the ears and palate, across the butterfly area of the face, and the bridge of the nose. As the patient gets older, the telangiectasia extends to the neck, the dorsum of the hands and feet, and in the antecubital and popliteal areas. The telangiectatic vessels originate from the subpapillary venous plexuses.
  • Vitiligo and premature graying of the hair have been observed. Other skin manifestations of AT are as follows: seborrheic dermatitis, atopic dermatitis, café au lait spots, scleroderma-like changes, and nummular eczema.
• Upper and lower respiratory tracts
• • Frequent sinopulmonary infections are common manifestations of AT. The onset of these frequent respiratory infections tend to occur at 4-6 years.
  • Recurrent bronchitis and sinusitis lead to bronchiectasis and pulmonary fibrosis. The recurrent respiratory infections are the cause of death during adolescence or young adulthood even with optimal antimicrobial and supportive treatment.
• Immune system
• • A common feature in AT is the deficiency of immunoglobulin A (IgA) associated with normal or elevated levels of immunoglobulin G (IgG) and immunoglobulin M (IgM). Normally, IgA represents approximately 90% of the globulin in nasal secretions and 5% of the serum globulin. Since nasal secretions are associated with antiviral activity and are deficient in AT, there appears to be a causal relationship to the susceptibility for respiratory infection observed in this syndrome.
  • Immunological abnormalities in AT include the following: decreased peripheral lymphoid tissue, stunted growth, lymphopenia, absence of delayed hypersensitivity, impaired skin homograft rejection, impaired circulating antibody response to some (weak) antigens, and impaired T-cell function. An elevated alpha-fetoprotein level, present in almost all patients with AT, often is associated with pathologic conditions of the liver and chronic hepatitis.
• Viscera: Hypoplasia or atrophy of the thymus gland is a characteristic finding in AT. This syndrome is associated with glucose intolerance and insulin resistance probably due to defects in the affinity of the receptors for insulin.

Physical

• The facies usually are dull, relaxed, and sad, but are in sharp contrast to the cheerful alert appearance when the child is made to smile.
• Hair and skin tend to be coarse and dry. Some gray hair is visible.
• Ataxia of stance and gait, greatly diminished tendon reflexes, dysmetria of the arm movements, decreased tone in the arms and legs, and flexor plantar reflexes are present.
• Vascular markings of the bulbar conjunctiva, external ears, nasal septum, butterfly of the face, and hard and soft palates are seen.
• Tympanic membranes usually are scarred and thickened.
• Postnasal drainage and drooling usually are present.
• Inspiratory and expiratory rales are present in the lungs.
• Testicular or ovarian atrophy is often present.

Causes

• DNA processing or repair protein is the suspected common denominator in this syndrome.
• AT is inherited as an autosomal recessive, and the gene for it has been localized to band 11q22-23.

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Hartnup disease
Cockayne syndrome
De Sanctis-Cacchione syndrome
Friedreich ataxia
Rendu-Osler-Weber disease

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Lab Studies

• Complete blood count
• Urinalysis and urinary amino acids
• Immunoglobulin panel
• Serum alpha fetoprotein level (raised in 90% of cases)

Imaging Studies

• Chest x-ray
• MRI of the brain

Other Tests

• Electrocardiogram
• Encephalogram

Histologic Findings

Histopathologic studies of the brain of an affected individual have revealed loss of Purkinje cells, granular cells, and basket cells of the cerebellar cortex.

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Medical Care

• Evaluation usually can be conducted on an outpatient basis.
• Management of recurrent sinopulmonary infections may require hospital stay and intravenous antibiotics.

Consultations

• Ophthalmology
• Neurology
• Genetics
• Otorhinolaryngology

Activity

• Limited by progression of truncal ataxia

FOLLOW-UP

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• Monitor respiratory infections.
• Physical therapy is indicated.

Complications

• Death
• Recurrent pulmonary infections
• Progressive ataxia leaves the patient wheelchair ridden.

Prognosis

• More than 50% of affected patients with AT die of recurrent respiratory infections, and many of the remainder develop malignancies, such as leukemia or lymphomas.

Patient Education

• Children should have psychologic counseling as they age because of the great disparity between chronological age and mental age in tests involving visual motor coordination.

MISCELLANEOUS

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to recognize associated conditions, such as recurrent respiratory infections, lymphoma, and leukemia

Special Concerns

• Careful evaluation of the eyes aids in the diagnosis since conjunctival telangiectasia eventually is present in all the cases.

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

• Albert DM, et al. Phakomatoses-Ataxia-Telangiectasia (Louis-Bar Syndrome). In: Principles and Practice of Ophthalmology Clinical Practice. Philadelphia: WB Saunders;1994.
• Boder E. Ataxia-telangiectasia: Familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasia, and frequent pulmonary infection. Pediatrics. 1958;21:526.
• Farr AK, Shalev B, Crawford TO. Ocular manifestations of ataxia-telangiectasia. Am J Ophthalmol. Dec 2002;134(6):891-6. [Medline].
• Fireman P, et al. Ataxia-telangiectasia: a dysgammaglobulinemia with deficient Gamma 1A (B2A) Globulin. Lancet. 1964;1:1193-5.
• Gatti RA, Berkel I, Boder E, et al. Localization of an ataxia-telangiectasia gene to chromosome 11q22-23. Nature. Dec 8 1988;336(6199):577-80. [Medline].
• Gatti RA, Boder E, Vinters HV, et al. Ataxia-telangiectasia: an interdisciplinary approach to pathogenesis. Medicine (Baltimore). Mar 1991;70(2):99-117. [Medline].
• Harley RD, Baird HW, Craven EM. Ataxia-telangiectasia. Report of seven cases. Arch Ophthalmol. May 1967;77(5):582-92. [Medline].
• Karpati G, et al. Ataxia-telangiectasia. Am J Dis Child. 1965;110:51.
• Lewis RF, Lederman HM, Crawford TO. Ocular motor abnormalities in ataxia telangiectasia. Ann Neurol. Sep 1999;46(3):287-95. [Medline].
• Lewis RF, Crawford TO. Slow target-directed eye movements in ataxia-telangiectasia. Invest Ophthalmol Vis Sci. Mar 2002;43(3):686-91. [Medline].
• Perlman S, Becker-Catania S, Gatti RA. Ataxia-telangiectasia: diagnosis and treatment. Semin Pediatr Neurol. Sep 2003;10(3):173-82. [Medline].
• Swift M, Reitnauer PJ, Morrell D, Chase CL. Breast and other cancers in families with ataxia-telangiectasia. N Engl J Med. May 21 1987;316(21):1289-94. [Medline].
• Tadjoedin MK, et al. Hereditary of Ataxia-Telangiectasia (Louis-Bar Syndrome). Amer J Dis Child. July 1965;110.

Article Last Updated: Jun 29, 2006